Exploration of carbonic anhydrase inhibition of bioactive metabolites from Pistacia integerrima by molecular docking and first-principles investigations

• Main Authors: Ahmad Irfan, Muhammad Imran, Sajjad H. Sumrra, Muhammad Naeem Qaisar, Noreen Khalid, Muhammad Asim Raza Basra, Asma Tufail Shah, Mohamed Hussien, Mohammed A. Assiri, Abdullah G. Al-Sehemi
• Format: Article
• Language: English
• Published: Elsevier 2021-10-01
• Series: Journal of Saudi Chemical Society
• Subjects: Pistacia integerrima; Anacardiaceae; Carbonic anhydrase; Pistacide A and B; Biological activity; Molecular docking
• Online Access: http://www.sciencedirect.com/science/article/pii/S1319610321001290

Bioassay guided fractionation of Pistacia integerrima crude methanolic extract gave Pistacide-A (1) and Pistacide-B (2), along with ten known phytochemicals (3–12). Biochemical analysis of crude plant extract, in-vitro and in-silico carbonic anhydrase inhibitory potential of newly isolated compounds Pistacide-A (1) and Pistacide-B (2) were performed. The cytotoxicity of extract in methanol, ethylacetate and n-butanol against Artemia salina brine-shrimp was 34.98 g/ml, 160.81 g/ml, and 135.77 g/ml, respectively. The significant antimicrobial activity was exhibited by crude, ethyl acetate, and n-butanol fractions. Compounds 1 (IC50 = 6.51 ± 0.42 mM) and 2 (IC50 = 2.85 ± 0.09 mM) showed good carbonic anhydrase inhibition compared with standard zonisamide drug (IC50 = 1.87 ± 0.003 mM). In addition, we have also clarified the electronic properties, absorption wavelengths, molecular electrostatic potential and Hirshfeld analysis by first-principles studies. The coherent intra-molecular charge transfer was seen from occupied to unoccupied molecular orbitals. The absorption wavelengths calculated at time dependent B3LYP/6-31G** level in methanol provided excellent accord with the experimental evidence. Molecular docking score revealed that Pistacide-B would be an efficient drug than its other counterpart that is rational to the experimental data.